This invention relates to aspirating and dispensing small volumes of liquids. In particular, it relates to automatic aspirating and dispensing of small volumes of liquids, typically for analytical purposes.
It is possible to accurately aspirate and dispense submicroliter volumes of liquid for analytical applications and to accurately verify the volume of liquid dispensed. The liquid may contain chemically or biologically active substances.
It is also possible to monitor in real time the dispensing of single 100 micron or smaller drops of liquid.
One of the primary factors for successful operation of micromachined or capillary-based piezoelectric-drop-on-demand technology is the ability to keep the dispensers clean.
Multiple technologies exist to clean the outside of the tips by flushing or jetting liquid at the orifice of the dispenser. Dispenser tips can also be immersed in ultrasonic baths to dislodge particles and molecules from the surface of the dispensers.
While these technologies are very effective at cleaning the outside of the dispenser, they do not thoroughly remove deposits adhering to the interior walls. A piezoelectric-drop-on-demand capillary has a very small bore orifice of approximately 5 to 100 xcexcm and, therefore, cannot be scrubbed by standard mechanical means like a brush or cloth.
Magnetic particles have been associated with various types of separation processes. In recent years magnetic particles have been used to adhere to biological materials to facilitate separation of such materials from the medium in which they are located. One example is found in U.S. Pat. No. 5,895,631 where a high molecular substance is bonded to magnetic particles, which are then attracted to the wall of a container by an external magnetic force. The particles could be removed by releasing the magnetic force which attached the particles to the wall and then flushing them from the container. Similarly, magnetic particles find a new use in the present invention which provides a means for cleaning the interior of the capillary tips used for dispensing 100 micron or smaller drops of liquid.
In accordance with one aspirating and dispensing apparatus, 1 to 100 micron range drops of liquid are accurately deposited onto various types of locations, typically for analytical purposes.
In another aspect, subnanoliter drops of liquid are dispensed and a pressure change resulting from the droplet ejection is detected. A known volume of a compressible fluid, e.g., a gas such as air, facilitates measuring small changes in system pressure which correlate to the volume of the transfer liquid which has been dispensed.
In accordance with still another aspect, subnanoliter drops of liquid are dispensed, and a pressure change resulting from ejection of a drop of a transfer liquid is detected by an electrical signal which indicates that single drops of liquid are dispensed at millisecond intervals. By eliminating all compressible fluids (gases) from the liquid in the system, the ejection of picoliter size drops can be detected. The dispensed drops are generally in the range of from about 5 to about 500 picoliters, often about 100 to about 500 picoliters.
Subnanoliter droplets of liquid are ejected and the volume of the drops can be measured in real time. Electrical signals indicating transient pressure changes in the transfer liquid upon dispensing liquid drops (in the range of from about 5 to about 500 picoliters, preferably about 100 to about 500 picoliters) can be detected when the liquid in the enclosed volume of the dispenser is connected to a liquid reservoir. As long as substantially all compressible fluids (gases) are kept out of the dispensing conduit (which communicates through a restricted passage to the liquid reservoir), the pressure sensor of the system of the present invention can detect dispensing a single drop of liquid in the range of from about 5 to about 500 picoliters, preferably about 100 to about 500 picoliters. The pressure change resulting from ejection of such a drop occurs in a time period long enough for the pressure change to be detectable, but short enough to complete the cycle before the next drop is ejected.
The invention particularly relates to a means for cleaning the interior of the capillary tubes used to dispense such small droplets, the cleaning being carried out by magnetic particles aspirated into the capillary tubes and moved by a magnet outside the capillary tubes to dislodge deposits adhering to the inner walls.
Other aspects of the present invention will become apparent to those skilled in the art upon studying this disclosure.